Liquid sample supply apparatus

ABSTRACT

A liquid sample supply apparatus including two reaction cells and means for withdrawing two samples from a single container and for delivering the samples simultaneously to the reaction cells. The invention is particularly useful for rate photometric analyses in which it is essential that equal samples be added to a blank reagent and total reagent simultaneously so that blank rates are the same in each reagent.

United States Patent [191 Hoffa et a1.

1 1 LIQUID SAMPLE SUPPLY APPARATUS [75] Inventors: Jack L. Hoffa, Brea; John ,I. Brown,

Fullerton, both of Calif.

[73] Assignee: Beckman Instruments Inc.,

Fullerton, Calif.

[22] Filed: Feb. 24, 1972 [21] Appl. No.: 228,905

[52] U.S. Cl.,.. 73/423 R, 23/253 R, 141/178 [51] Int. Cl. G01n l/10 [58] Field of Search 23/253, 259; 73/423 A, 73/423 R; 141/130, 178, 179

[56] References Cited UNITED STATES PATENTS 2,932,330 4/1960 Donofrio 141/178 3,081,158 3/1963 Winter.... 23/259 X 3,252,330 5/1966 Kling 23/253 R Dec. 10, 1974 3,542,515 11/1970 Scott 23/253 R X 3,617,222 l1/1971 Matte 23/253 R X FOREIGN PATENTS OR APPLICATIONS 1,539,674 8/1968 France 23/253 R X Primary Examiner-Morris O. Wolk Assistant ExaminerTimothy W. Hagan Attorney, Agent, or FirmR. .l. Steinmeyer [5 7 ABSTRACT A liquid sample supply apparatus including two reaction cells and means for withdrawing two samples from a single container and for delivering the samples simultaneously to the reaction cells. The invention is particularly useful for rate photometric analyses in which it is essential that equal samples be added to a blank reagent and total reagent simultaneously so that blank rates are the same in each reagent.

9 Claims, 5 Drawing Figures 1 I LIQUID SAMPLE SUPPLY APPARATUS BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid sample supply apparatus for supplying liquid sample automatically to a liquid'analysis apparatus.

The present invention is particularly applicable to in- AELC where E is the unknown enzyme that is to be determined. Since in many cases there is no convenient way to continuously measure the formation of B or the disappearance of A, a second or auxiliary enzyme is added to convert B to C which can be continuously measured. For example C is often the substance NADH which absorbs light at 340 nm and can thus be measured in a UV spectrophotometer. These systems are structured so that reaction (2) is much faster than reaction (1) so that the rate of formation of C is directly proportional to the amount of unknown, E present. However,'in such a complex system there are several possibilities for blank reactions which add to the rate of reaction (2) but which are not related to the amount of E present.

For example if B is present in the sample, reaction (2) from the total rate of a complete reaction mixture to give a more correct value for E Now in a double beam spectrophotometer the blank reation can be placed in v the reference beam and it will then be automatically subtracted from the total reaction rate by the nature of the double beam measurement. A complicating factor is that since the blank reaction rate is proportional to the amount of B present, the blank rate slows down as B is consumed. Thus it is essential that sample be added to both the blank reagent and the total reagent simultaneously so that the blank rates are the same in each. The same analysis applies to enzyme assay systems using two auxiliary enzymes and to cases where C is consumed or generated by a third enzyme, E What is needed therefore and constitutes the object of the present invention is a liquid sample supply apparatus for transferring equal samples from a single sample container to two separate reaction cells simultaneously.

DESCRIPTION OF THE PRIOR ART A wide variety of sample supply devices for automatic chemical analyzers are known in the art. Examples of such devices are disclosed in the following U.S. Pat. Nos. 3,038,340; 3,134,263, 3,230,776;'3,25I,229; 3,252,329; and 3,430,495. In each of the devices disclosed in these patents, a single pick-up probe is utilized for withdrawing sample from a sample container and delivering sample to a reaction or analysis cell or for transferring sample from one container to another. To our knowledge, the prior art does not disclose an apparatus suitable for transferring two equal samples from a container to two separate reaction cells simultaneously which is required for the rate enzyme analyses discussed hereinbefore.

SUMMARY OF THE INVENTION According to the principal aspect of the present invention, there is provided a liquid sample supply apparatus including two reaction cells and means for with drawing two samples from a single container and for delivering the samples simultaneously to the reaction cells. In the preferred form of the invention, such apparatus comprises a pair of sample pick-up probes and means for sequentially moving the probes into and out of the sample container, shifting the probes laterally of the container, laterally displacing the probes relative to each other and thereafter moving each of the probes simultaneously into the reaction cells for delivering equal samples simultaneously to the cells.

BRIEF DESCRIPTION OF THE DRAWINGS DESCRIPTION OF THE PREFERRED v EMBODIMENT Referring now to the drawings in detail, the apparatus of the present invention, generally designated 10, which may comprise a spectrophotometer or other analytical instrument, includes a housing 12 formed with an opening 14 in one side thereof. A pair of reaction cells l6and 18 are positioned in horizontal spacedapart relationship within the housing remote from the opening 14, as seen in FIG. 2. A' sample container 20 is adapted to be-mounted by any suitable means, not shown, outside the housing 12 adjacent to the opening 14. A pair of flexible tubes 22 and 24 are mounted in relatively rigid vertical supports 26 and 28, respectively, which are carried by a mechanism to be described in detail later. The lower ends of the tubes 22 and 24 extend below the ends of the supports 26 and 28 to form sample pick-up probes 30 and 32, respectively. As shown in FIGS. 1 and 2, the sample container 20 is positioned below the probes 30 and 32 in vertical alignment therewith, and the probes are positioned sufficiently close to each other so that when they are lowered by a mechanism to be disclosed in detail later, they will enter together into the container to become immersed in the sample 34 held therein.

The mechanism for imparting motion to the probes in accordance with the present invention includes a base 36 mounted within the housing I0. A pivot shaft 38 is mounted vertically in the base 36 and is journaled for rotation about its longitudinal vertically extending axis by means of bearings and 42. A generally horizontally extending plate 44 is fixedly mounted on the top of the base 36. An elongated drive arm 46 is fixed to the shaft 38 by a set screw 47 and, hence, is rotatable about such axis in a horizontal plane. A gear 48 concentric with the shaft 38 is located below the arm 46. The gear is fixedly connected to the arm by means of countersunk screws 50, only one being shown. A washer 52 is interposed between the lower surface of the gear 48 and the upper surface of the plate 44. The teeth on the gear 48 engage the teeth of a gear 54 fixed to a vertically disposed drive shaft 56 of a motor 58 attached to the plate 44. A bushing 60 isrotatably mounted on the shaft 38 above the arm 46. A second elongated arm 62 is pivotally mounted on the bushing 60 so as to be rotatable in a horizontal plane relative to the longitudinal axis of the vertical shaft 38. The bushing 60 is formed with an outwardly extending flange 64 at its lower end which forms a bearing support between the arms 46 and 62. As will be appreciated, when the motor 58 is energized to rotate the shaft 56 in a counterclockwise direction as seen in FIG. 2, the gear 48 will be rotated in a clockwise direction to pivot the drivearm 46 in a horizontal plane about the longitudinal axis of shaft 38.

A-pair of vertically extending cylindrical guide shafts 66 and 68 are fixedly mounted adjacent the end 69 of the arm 62 remote from the pivot shaft 38. The upper ends of the shafts 66 and 68 extend through openings in a support plate 70 which is fixedly attached to the shafts by means of set screws 72 and 74.

A pair of generally L-shaped horizontally disposed probe support elements 76 and 78 are mounted for common vertical sliding movement on the guide shaft 166 by means of a bushing assembly 80. As best seen in FIG. l, the element 76 is positioned above the element 78.,The bushing assembly 80, as best seen in FIG. 3, includes an inner bushing 82 and an outer bushing 84. The inner bushing is rotatable with respect to the shaft 66 and outer bushing 84. The inner bushing is formed 1 with an outwardly extending annular flange 86 at its lower end which supports the lower element 78. Outer bushing 84 is formed at its lower end with an outwardly extending annular flange 88 which provides a bearing surface between the lower surface of the upper element 76 and the upper surface of the lower element 78. The upper element 76 is fixedly connected to the outer bushing 74 by means of a set screw 90. A retaining ring or snap ring 92 is mounted in an annular groove 94 formed in the inner bushing 82 adjacent its upper end 96 so that the bushings 82 and 84, and hence the elements 76 and 78, will move together vertically on the shaft 66 when one of such elements is shifted vertically.

The second guide shaft 68 extends through an opening 96 in the upper element 76 so that such element is nonpivotally mounted with respect to the shaft 66. However, because the inner bushing 82 of bushingassembly is rotatable with respect to both the guide shaft 6 and the outer bushing 84, the lower element 78 may be pivotally rotated about the shaft 66 independent of the upper element 76.

The outer leg 100 of the upper L-shaped element 76 and the outer leg. 102 of the lower L-shaped element 78 are generally perpendicular to the elongated arms 62 and 46. The probe support 26 is fixedly mounted in the outer end of leg 102 while probe support 28 is fixedly mounted in the outer end of leg 100. Thus, when the arms 46 and 62 are disposed in the position illustrated in full lines in FIG. 2, thie legs 100 and 102 of the upper and lower. elements 76 and 78 respectively will. extend outwardly through the opening 14 in the housing 12 so that the sample pickup probes carried by the probe supports 26 and 28 will bedisposed ovver the sample container 20.

The elements 76 and 78 are movable vertically on the guide shaft 66 by means of a motor 104 fixedly mounted on top of the arm 62. The motor has a horizontally disposed drive shaft 106 carrying a gear 108 which engages a second gear 1 10 rotatably mounted on a horizontally extending shaft. 112 carried by a frane 114. An elongated arm 116 is fixedly connected to the gear by means of screws 117 and 118. The outer end of the arm 1 16 is formed with an elongated slot 119 which receives a horizontally disposed pin 120 fixedly connected to the upper element 76. Thus, when the motor shaft 106 is rotated clockwise as viewed in FIG. 1, the gear 110 will rotate counterclockwise so that the outer end of the arm 1 16 will drop thereby lowering the elements 76 and 78 which carry the sample pick-up probes. Reversal of the motor 104 will of course raise such elements on the shaft 66. 1

As best seen in FIG. 1, the outer end 122 of the drive arm 46 extends beyond the end 69 of the arm 62. A vertically extending drive post or rod 124 is fixedly connected to the arm 46 adjacent to the end 122. The upper end of the drive post 124 extends through an elongated slot 126 in the lower element 78. Such slot extends generally radially from the axis of rotation of the pivot shaft 38. The post 124 therefore provides a driving connection between the drive arm 46 and the upper element 78 which is pivotally'mounted with respect to the guide shaft 66. Thus, when the arm 46 is rotated by the motor 58 in a clockwise direction as viewed in FIG. 2, the drive post 124 carried by such arm will initially causev the lower element 78 to pivot in a horizontal plane about the guide shaft 66 and, upon further rotation of the arm, the post will pull both elements 76 and 78 as well as the arm 62in acounterclockwise direction until-the arms engage stopmeans carried by a bracket 130 fixed to the plate 44.'Since the element 78 is pivoted relative to the element 76, the outer ends of the legs 102 and 100 of such elements will spread apart, as seen in FIG. 2, thus separating laterally the sample pick-up probes 30 and 32.

As best seen in FIGS. 2, 4 and 5, the bracket 130 carries a pair of horizontally'disposed set screws 132 and 134. The screw 132 is disposed in the same plane as the arm 62 while the screw 134 is disposed in the same plane as the drive arm 46. The'outer end 136 of screw 132 extends beyond the outer end 138 of screw 134 so that rotation of arm 62 will be ceased prior to rotation of arm 46. Theexact position of the ends 136 and 138 of the set screws 132 and 134, respectively, are set such that the sample pick-up probes 30 and 32 will be disposed in exact vertical alignment over the reaction cells 16 and 18 when the arms 62 and 46 are disposed in the'phantom-line position illustrated in FIG. 2 wherein such armsengage the ends of the set screws. The bracket 130 also carries a microswitch 140 having an actuating am 141 disposed in the same plane as the drive arm 46.

A second bracket 142 is mounted on the plate 44 opposite the bracket 130. This bracket also carries a pair of horizontally disposed set screws 144 and 146. The set screw 144 is disposed in the same plane as the arm 62 while the set screw 146 is disposed in the same plane as arm 46. These screws are set so that the sample pickup probes 30 and 32 will be appropriately positioned to extend into the sample container when the arms 46 and 62 are located in the position shown in full lines in FIG. 2. The bracket 142 also carries a microswitch 148 having an actuating arm 150 disposed in the plane of the drive arm 46 for engagement therewith. An additional microswitch 152 is mounted on the arm 62 with its actuating arm 154 disposed in the path of vertical movement of the lower element 78. Still a further microswitch 156 is mounted on the plate 711 with its actuating arm 168 disposed in the path of vertical movement of the upper element 76. The purposes of these switches will become more apparent from the following description.

One cycle of operation of the apparatus 11) will now be described. The cycle commences with the arms 46 and 62 and the pick-up probe carrying elements 76 and 78 positioned as shown in phantom in FIG. 2, with the sample pick-up probes and 32 in their up position above the reaction cells 18 and 16. A control circuit, not shown, including the microswitches 140, 148, 152 and 156, is energized manually, thereby energizing the motor 58 to rotate the drive arm 46 in the counterclockwise direction as viewed in FIG. 2. Normally there will be sufficient frictional engagement between the arms 46 and 62 by virtue of the bushing 60 interposed therebetween to cause the two arms to rotate together. However, if insufficient friction exists between these parts, the drive arm 46 will rotate independently of the arm 62 for a short distance until the upper end of probe support 26 engages the rear surface 160 of element 76, whereupon such arms and elements will pivot together about the longitudinal axis of pivot shaft 38 until the arms 46 and 62 engage the set screws 146 and 144. At this time the various parts take the position illustrated in full lines in FIG. 2, wherein the sample pick-up probes 30 and 32 are positioned outside of the housing 12 in vertical alignment over the sample container 20. At the same instance the actuating arm 150 of microswitch 148 is engaged by the drive arm 46 thereby deenergizing the motor 58 and energizing the motor 104. When motor 104 is energized at this instance, the gear 108 carried by the drive shaft 106 of the motor is rotated in a clockwise direction so that the end of the arm 116 will be lowered thereby lowering the elements 76 and 78 together so that the sample pick-up probes 32 and 30 will be immersed simultaneously into the sample 34 in the container 20. When the element 78 reaches its lowermost position, it will engage the actuating arm 154 of microswitch 152 thereby deenergizing motor 104 and energizing a pump, connected to tubes 22 and 24, to draw sample up into the pick-up probe 30 and 32. The details of the pump mechanism is not disclosed herein since such is conventional. Upon completion of the pump intake phase, the control circuit energizes motor 104 to rotate its drive shaft 106 in counterclockwise direction thus effecting the raising of the elements 76 and 78, and thus vertical withdrawal of the pick-up probes from the sample container 20. When the upper element 76 reaches its uppermost position, it engages the actuating arm 158 of microswitch 156 thereby de-energizing the motor 104 and energizing motor 58 to translate the arms 46 and 62 in a horizontal plane in a clockwise direction as viewed in FIG. 2 about the longitudinal axis of pivot shaft 38. As the arms approach the bracket 130, the upper arm 62 will engage the set screw 132 and thereafter the lower arm 46 will engage the set screw 134 and switch arm 141. As the two arms are rotated during this period, the element 78 is pivoted laterally with respect to the element 76 thereby spreading the probe supports 26 and 28 apart so that when the arms engage set screws 132 and 134 such supports, and therefore the sample pick-up probes 30 and 32, will be disposed in exact vertical alignment over the reaction cells 18 and 16. Engagement of the switch arm 141 deenergizes the motor 58 and energizes the motor 104 to lower the sample pick-up probes simultaneously into the reaction cells. At the same time, the control circuit energizes the pump assembly, not shown, which expels sample simultaneously into the reaction cells. At completion of the pumping cycle, the motor 104 is again energized by the control circuit to raise the probes out of the reaction cell, thus completing one full cycle of operation of the apparatus.

Thus, it can be seen that by the present invention there is provided an apparatus which allows the withdrawal of two like samples from a single container and the delivery of the samples simultaneously to two separate reaction cells. Because of the particular mounting of the elements 76 and 78 on the guide shafts 66 and 68, and the mechanism for raising and lowering such elements, the sample probes travel vertically in a straight, rather than in an arcuate path. Thus, the probes may be disposed in sample containers having an internal diameter as small as 10 mm. This feature is important when only very small samples are available, which is frequently encountered in the analysis of biological fiuids. Also, by the arrangement of the present invention, the horizontal and vertical travels of the sample probes are independent so that such travels can be programmed in and out of the reaction cells for both sample delivery and probe washing cycles. If the invention is employed for spectrophotometric analysis, it is normally desirable to isolate the reaction cells from the exterior of the housing so that no light from outside the housing will interfere in the analyses. Therefore, a suitable closure (not shown) could be provided for closing the opening 14 when the sample pick-up probes are disposed inside the housing.

Although only a single embodiment of the invention has been disclosed herein for purposes of illustration, it will be understood that various changes can be made in the form, details, arrangement and proportions of the various parts in such embodiment without departing from the spirit and scope of the invention as defined by the appended claims.

What is claimed is:

1. A liquid sample supply apparatus for transferring two samples from a single container to two separate reaction cells simultaneously having a pair of vertically extending probes for insertion into the single container, means for lifting them vertically simultaneously, transporting them horizontally thereafter while horizontally separating them and thereafter positioning them over the horizontally separated reaction cells to discharge liquid drawn from the sample supply into said horizontally separated reaction cells wherein the invention comprises:

two horizontally and vertically movable probe support elements, one pivoted to the other,

a pair of horizontally movable pivoted arms,

means connecting one of said arms to one of said probe support elements, the probe support elements each supporting one of said probes at an end of the element space from the pivotal joint between them whereby the probes are capable of horizontal separation and relative horizontal movement.

2. An apparatus as set forth in claim 1 wherein said probes are caused to translate in a longitudinal plane when shifted laterally by said motion imparting means, and said means effects the vertical and horizontal travel of said probes independently.

3. An apparatus as set forth in claim 2 including adjustable stop means engageable by said motion imparting means for controlling the extent of horizontal travel of said probes.

4. An apparatus as set forth in claim 1 wherein the horizontally pivoted:

arms are each mounted for pivotal movement in a generally horizontal plane about a substantially vertically extending axis;

and the apparatus includes:

vertical guide means carried by a first of said arms;

means for pivoting the second of said arms about said axis; and

means for raising and lowering said probe support elements on said guide means.

5. An apparatus as set forth in claim 4 wherein said first arm is disposed in a plane above said second arm and one of said probe support elements is disposed in a plane above the other probe support element.

6. An apparatus as set foroth in claim 5 wherein said connecting means comprising a vertically extending rod carried by said second arm, an elongated slot is provided in one probe support element extending generally radially from said axis, and the upper end of said rod being slidably received in said slot.

7. An apparatus as set forth in claim 4 wherein said probe support elements have a generally L-shaped configuration, with one leg of each L-shaped element extending generally perpendicular to said arms, and said probes each being mounted adjacent the end of the extending leg of an L-shaped element.

8. An apparatus as set forth in claim 1 wherein:

the horizontally pivoted arms are mounted one above the other as upper and lower arms each mounted for pivotal movement in a generally horizontal plane about a substantially vertically extending axis;

a vertically extending guide shaft is provided which is fixedly mounted on said upper arm;

the probe support elements being mounted one above the other as upper and lower elements carrying one of said probes, said upper and lower probe support elements being mounted for common vertical movement on said guide shaft, said upper element being non-pivotally mounted to said guide shaft and said lower element being pivotably mounted on said guide shaft for movement in a rod being slidably received in said slot. 

1. A liquid sample supply apparatus for transferring two samples from a single container to two separate reaction cells simultaneously having a pair of vertically extending probes for insertion into the single container, means for lifting them vertically simultaneously, transporting them horizontally thereafter while horizontally separating them and thereafter positioning them over the horizontally separated reaction cells to discharge liquid drawn from the sample supply into said horizontally separated reaction cells wherein the invention comprises: two horizontally and vertically movable probe support elements, one pivoted to the other, a pair of horizontally movable pivoted arms, means connecting one of said arms to one of said probe support elements, the probe support elements each supporting one of said probes at an end of the element space from the pivotal joint between them whereby the probes are capable of horizontal separation and relative horizontal movement.
 2. An apparatus as set forth in claim 1 wherein said probes are caused to translate in a longitudinal plane when shifted laterally by said motion imparting means, and said means effects the vertical and horizontal travel of said probes independently.
 3. An apparatus as set forth in claim 2 including adjustable stop means engageable by said motion imparting means for controlling the extent of horizontal travel of said probes.
 4. An apparatus as set forth in claim 1 wherein the horizontally pivoted: arms are each mounted for pivotal movement in a generally horizontal plane about a substantially vertically extending axis; and the apparatus includes: vertical guide means carried by a first of said arms; means for pivoting the second of said arms about said axis; and means for raising and lowering said probe support elements on said guide means.
 5. An apparatus as set forth in claim 4 wherein said first arm is disposed in a plane above said second arm and one of said probe support elements is disposed in a plane above the other probe support element.
 6. An apparatus as set foroth in claim 5 wherein said connecting means comprising a vertically extending rod carried by said second arm, an elongated slot is provided in one probe support element extending generally radially from said axis, and the upper end of said rod being slidably received in said slot.
 7. An apparatus as set forth in claim 4 wherein said probe support elements have a generally L-shaped configuration, with one leg of each L-shaped element extending generally perpendicular to said arms, and said probes each being mounted adjacent the end of the extending leg of an L-shaped element.
 8. An apparatus as set forth in claim 1 wherein: the horizontally pivoted arms are mounted one above the other as upper and lower arms each mounted for pivotal movement in a generally horizontal plane about a substantially vertically extending axis; a vertically extending guide shaft is provided which is fixedly mounted on said upper arm; the probe support elements being mounted one above the other as upper and lower elemEnts carrying one of said probes, said upper and lower probe support elements being mounted for common vertical movement on said guide shaft, said upper element being non-pivotally mounted to said guide shaft and said lower element being pivotably mounted on said guide shaft for movement in a horizontal plane; means are provided connecting said lower arm to said lower probe support element; and the apoparatus includes means for pivoting said lower arm relative to the upper arm about said axis; and means for raising and lowering said probe support elements on said guide shaft.
 9. An apparatus as set forth in claim 8 wherein said connecting means comprises a vertically extending rod carried by said lower arm, an elongated slot is formed in said lower probe support element extending generally radially from said axis, and the upper end of said rod being slidably received in said slot. 